Outline

C-reactive protein (CRP) represents the classical acute-phase protein produced in the liver in response to inflammatory stimuli. The present study investigated the association of DNA variants within the CRP gene and genes more upstream in the inflammatory cascade with differences in CRP concentrations and assessed its intra-individual variability as a marker of individual response. 1,003 myocardial infarction (MI) survivors were recruited in six European cities and CRP concentrations were measured repeatedly during a 6 month period. We investigated 114 polymorphisms in thirteen genes, all involved in the innate inflammatory pathway. We found two polymorphisms within the CRP gene, rs1800947 and rs1205, of which the minor alleles were strongly associated with lower levels of CRP (p<1.0e-06). A haplotype, identified by those two polymorphisms, was associated with the lowest CRP concentrations (p<1.0e-06). Additionally, the minor allele of a rare variant (rs1800894) in the promoter region of the interleukin-10 (IL10) gene was significantly associated with greater individual variability of CRP concentrations (p<1.0e-03).

The present study investigated the association of polymorphisms with inter- and intra-individual variability of CRP levels. Two minor alleles of CRP variants where associated with lower CRP concentrations. Regarding intra-individual variability, we observed an association with the minor allele of a variant in the promoter of the anti-inflammatory cytokine IL10.